A Study to Investigate the Pharmacokinetics of Ethinyl Estradiol and Levonorgestrel When Given Alone and in Combination With Baxdrostat in Healthy Females of Non-childbearing Potential
- Registration Number
- NCT06657105
- Lead Sponsor
- AstraZeneca
- Brief Summary
The main purpose of the study is to assess the effect of multiple doses of baxdrostat on the pharmacokinetics (PK) of a single dose of combined oral ethinyl estradiol (EE) and levonorgestrel (LNG). Safety and tolerability of baxdrostat will be assessed during the study.
- Detailed Description
This is an open-label, 3-period fixed sequence study conducted at a single Clinical Unit.
The study will comprise of:
* A Screening period of maximum 28 days.
* Period 1: - From Day -1 to Day 5.
* Period 2: -From Day 6 to Day 16
* Period 3: - From Day 17 to Day 23.
* A Final Follow-up Visit, 7 (± 2) days after the last PK sample in Period 3.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 22
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Females must have a negative pregnancy test at the Screening Visit and Study Day -1 (admission to Clinical Unit) and must not be lactating and must be of non-childbearing potential, confirmed at Screening by fulfilling one of the following criteria:
- Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range (Follicular Stimulating Hormone (FSH) > 40 mIU/mL).
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion.
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Have a Body Mass Index (BMI) between 18 and 30 kg/m2
- History of any clinically important disease or disorder which, in the opinion of the Investigator
- History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Sex hormone therapy within one month before study.
- History of drug-related hepatic toxicity.
- History or family history of potential risk of arterial and venous thromboembolic events (eg, factor V Leiden mutation).
- History of cardiovascular risk (eg, history of myocardial infarction).
- Any laboratory values with the following deviations at the Screening Visit and Study Day -1 (admission to Clinical Unit).
- Any positive result on screening for serum HBsAg, HBcAb, HCV or HIV.
- History of any treatment with QT prolongation drugs.
- Current smokers or know history of alcohol or drug abuse.
- History or ongoing severe allergy/hypersensitivity.
- An increased risk for developing SAEs or a contraindication associated with administration of EE, or LNG such as history of thrombosis or thromboembolism, presence of estrogen dependent tumors, hypertension, migraines, and liver disease.
- Participants treated with strong CYP3A4 inhibitors or inducers within 3 months or longer (5 half-lives) prior to first administration of IMP in this study.
- Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days or 5 half-lives (whichever is longest) of the first administration of IMP in this study.
- Participants who are vegans or have medical dietary restrictions and vulnerable participants.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Period 3: Baxdrostat + EE/LNG Baxdrostat Participants will receive baxdrostat once daily on Day 17 to Day 22 and will receive EE+LNG in the fasted state on Day 18, followed by oral dose of EE/LNG PK sampling for 120 hours (EE=72 hours and LNG=120 hours). Period 1: Ethinyl estradiol/Levonorgestrel (EE/LNG) EE/LNG Participants will receive oral dose of EE/LNG in the fasted state on Day ,1 followed by PK sampling of EE/LNG for 120 hours (EE 72 hours and LNG 120 hours). Period 2: Baxdrostat Baxdrostat Participants will self-administer the baxdrostat tablet once a day from Day 6 to Day 16. Period 3: Baxdrostat + EE/LNG EE/LNG Participants will receive baxdrostat once daily on Day 17 to Day 22 and will receive EE+LNG in the fasted state on Day 18, followed by oral dose of EE/LNG PK sampling for 120 hours (EE=72 hours and LNG=120 hours).
- Primary Outcome Measures
Name Time Method Area under concentration-time curve from time zero to infinity (AUCinf) EE: Up to Day 21, LNG: Up to Day 23 To assess the effect of multiple doses of baxdrostat on the PK of a single dose of combined oral EE/LNG in healthy females of non-childbearing potential.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) EE: Up to Day 21, LNG: Up to Day 23 To assess the effect of multiple doses of baxdrostat on the PK of a single dose of combined oral EE/LNG in healthy females of non-childbearing potential.
Maximum observed drug concentration (Cmax) EE: Up to Day 21, LNG: Up to Day 23 To assess the effect of multiple doses of baxdrostat on the PK of a single dose of combined oral EE/LNG in healthy females of non-childbearing potential.
- Secondary Outcome Measures
Name Time Method Maximum observed drug concentration (Cmax) of EE/LNG EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of EE/LNG EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Time to reach maximum observed concentration (tmax) EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Terminal elimination half-life (t1/2λz) EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Terminal rate constant (λz) EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUCinf (RAUCinf) EE: Up to Day 21, LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Ratio of EE or LNG to EE (alone) or LNG (alone) based on AUClast (RAUClast) EE: Up to Day 21; LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Ratio of EE or LN to EE (alone) or LNG (alone) based on Cmax (RCmax) EE: Up to Day 21; LNG: Up to Day 23 To describe the PK of a single dose of combined oral EE and LNG in healthy females of non-childbearing potential.
Number of participants with adverse event (AEs) From screening (Day -28 to Day -2) to 8.5 weeks To examine the safety and tolerability of baxdrostat alone and in combination with combined oral EE and LNG.
Maximum observed drug concentration (Cmax) of Baxdrostat Baxdrostat: Day 18 to Day 22 To assess the PK of baxdrostat in healthy female participants of non-childbearing potential.
Observed lowest concentration before the next dose is administered (Day 22 pre-dose) (Ctrough) Baxdrostat: Day 18 to Day 22 To assess the PK of baxdrostat in healthy female participants of non-childbearing potential.
Trial Locations
- Locations (1)
Research Site
🇺🇸Brooklyn, Maryland, United States
Research Site🇺🇸Brooklyn, Maryland, United States